Carcinogenesis Advance Access published online on March 31, 2005
Carcinogenesis, doi:10.1093/carcin/bgi082
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1 Institute of Nutritional Physiology, Federal Research Centre for Nutrition and Food, Haid-und-Neu-Str. 9, 76131 Karlsruhe, Germany
* To whom correspondence should be addressed. Clear (CleA) and cloudy (CloA) apple juices containing different amounts of analyzed procyanidins and pectin were investigated for colon cancer-preventive effects and underlying molecular mechanisms in F344 rats given i.p. injections of 1,2-dimethylhydrazine (DMH; 20 mg/kg body wt) once weekly for 4 weeks. Rats received either water (Cont), CleA or CloA (ad libitum) for 7 weeks starting one week before the first DMH-injection. CloA inhibited DMH-induced genotoxic damage in mucosa cells of the distal colon compared to Cont as investigated by single cell microgel electrophoresis assay. The mean tail intensity in mucosa cells of DMH-treated controls (Cont/DMH: 6.1 ± 0.9 %) was significantly reduced by CloA (2.4 ± 0.8 %; p<0.01) but not by CleA intervention (4.1 ± 1.2 %; p>0.05). The crypt cell proliferation index induced by DMH (Cont/NaCl: 10.0 ± 0.7 %; Cont/DMH: 19.9 ± 1.0 %; p<0.001) was significantly decreased by CleA (15.7 ± 0.7 %; p<0.001) and CloA intervention (11.9 ± 0.4 %; p<0.001). CloA but not CleA significantly reduced the number of large aberrant crypt foci (ACF) consisting of more than 4 aberrant crypts (AC) (Cont/DMH: 37.4 ± 5.4; CleA/DMH: 32.8 ± 4.4, p>0.05; CloA/DMH: 18.8 ± 2.5 ACF; p<0.05) and the over-all mean ACF size in the distal colon (Cont/DMH: 2.31 ± 0.09; CleA/DMH: 2.27 ± 0.05; CloA/DMH: 2.04 ± 0.03 AC/ACF; p<0.05). After treatment with DMH and/or apple juices there were no changes in transcript levels of colonic cyclooxygenase isoforms (COX-1, COX-2) or glutathione-associated enzymes (GST-M2,
Received January 25, 2005
Revised February 28, 2005
Accepted March 22, 2005
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
Cloudy apple juice decreases DNA-damage, hyperproliferation and aberrant crypt foci development in the distal colon of DMH-initiated rats
2 Research Institute Geisenheim, Department of Wine Analysis and Beverage Research, 65366 Geisenheim, Germany
3 Institute of Nutritional Physiology, Federal Research Centre for Nutrition and Food, Haid-und-Neu-Str. 9, 76131 Karlsruhe, Germany; Technical University of Munich, Department of Food and Nutrition, 85354 Freising-Weihenstephan, Germany
S. W. Barth, E-mail: stephan.barth{at}bfe.uni-karlsruhe.de
Abstract 
-GCS, GST-P), the splenocyte natural killer cell activity and plasma antioxidant status. However, CloA but not CleA prevented the DMH-induced reduction of splenocyte CD4/CD8 (T-helper cells/cytotoxic lymphocytes) ratio. Since both formulations contained comparable concentrations and types of monomeric polyphenols, complex polyphenols or non-polyphenolic compounds such as pectin might be responsible for the stronger cancer-preventive effect by CloA.
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